CTRI/2024/08/072567 [Registered on: 16/08/2024] Trial Registered Prospectively
Last Modified On:
27/11/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Other
Public Title of Study
ALT-P1 Compared to Daily Growth Hormone Treatment of GENOTROPIN® (Somatropin) for Injection in Growth Hormone Treatment naive Prepubertal with Growth Hormone Deficiency.
Scientific Title of Study
A Randomized, Multicenter, Active-controlled Openlabelled, Multiple-Dose, Dose Finding, Parallel Group Trial, Investigating the Efficacy, Safety, Immunogenicity, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Different Weekly Doses of ALT-P1 Compared to Daily Growth Hormone Treatment of GENOTROPIN® (Somatropin) for Injection in Growth Hormone Treatment naive Prepubertal Children with Growth Hormone Deficiency.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.: C2A03447 Version: 02 Date: 15 Mar 24
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President - Global Clinical Operations
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad-382210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
2717698500
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director - II
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad-382210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
07966219500
Fax
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Devesh Verma
Designation
Director
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad-382210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
09712908404
Fax
Email
dverma@cliantha.com
Source of Monetary or Material Support
Cristália Produtos QuÃmicos Farmacêuticos Ltda
Primary Sponsor
Name
Cristália Produtos QuÃmicos Farmacêuticos Ltda
Address
Rodovia Itapira/Lindóia, Km 14, City of Itapira, State of São Paulo, Brazil
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Cliantha Research Limited
Cliantha Corporate, TP 86, FP 28/1, Off S P Ring Road, Sarkhej Ahmedabad - 382210 Gujarat, India
N-6 CIDCO, Aurangabad - 431003, Maharashtra, India Aurangabad MAHARASHTRA
9823896796
hphatale@gmail.com
Dr Arjun Baidya
Nilratan Sircar Medical College and Hospital
PI Room, 2nd floor, Department of Endocrinology, Nilratan Sircar Medical College and Hospital,138, Acharya Jagadish Chandra Bose Road, Kolkata – 700014, West Bengal, India.
Kolkata WEST BENGAL
9433154618
arjun.baidya@gmail.com
Dr Hardeva Ram Nehara
S.P Medical College and AG of Hospitals
Dept. of Endocrinologist, S.P Medical College and AG of Hospitals, Bikaner - 334003, Rajasthan Bikaner RAJASTHAN
three different weekly doses of 0.4, 0.6, and 0.8mg/kg/week for (Week 1/Day 1 to Week 28/Day 190)
Comparator Agent
GENOTROPIN® (Somatropin)
Daily dose of 0.24 mg/kg/week or 0.034 mg/kg/day for (Day 1 to Day 196)
Inclusion Criteria
Age From
2.00 Year(s)
Age To
11.00 Year(s)
Gender
Both
Details
Age:
For boys: age at least 2 years and 26 weeks and below or equal to 11.0 years at screening.
For girls: age at least 2 years and 26 weeks and below or equal to 10.0 years at screening.
1. Boys: Tanner stage 1 for pubic hair and testis volume below 4 ml, age at least 2 years and 26 weeks and below or equal to 11.0 years at screening
Or
Girls: Tanner stage 1 for breast development (no palpable glandular breast tissue) and pubic hair, age at least 2 years and 26 weeks and below or equal to 10.0 years at screening.
2. Confirmed diagnosis of growth hormone deficiency (GHD) within 12 months prior to screening as determined by two different growth hormone (GH) stimulation tests (any two tests from clonidine, insulin, glucagon, arginine and GHRH), defined as a peak GH level of below or equal to 7.0 ng/ml. For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed.
3. No prior exposure to GH therapy and/or insulin-like growth factor-1(IGF-1) treatment.
4. Bone age not greater than chronological age (CA) at the time of screening (on the basis of x-rays of the left hand and wrist).
5. Impaired height and Height Velocity at the time of screening. Impaired height defined as: Height of at least 2.0 standard deviations below the mean height for CA and gender according to the standards of WHO 2006 & Indian academy of pediatrics (IAP) 2015 combined Girls/Boys charts 0-18 years: Girls/Boys stature-for-age and weight-for-age percentiles at screening. Impaired height velocity defined as: Annualized height velocity (HV) below the 25th percentile for CA and gender or below -0.7 standard deviation (SD) score for CA and sex, according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months.
6. Body mass index (BMI) within ±2 standard deviation at the time of screening for the chronological age and sex according to the 2000 Centers for Disease Control and Prevention standards.
7. IGF-1 level of at least 1 standard deviation below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1) according to the central laboratory reference values at the time of screening.
8. Children with normal report of fundoscopy at the time of screening.
9. Children with multiple hormonal deficiencies must be on stable replacement therapy (other than hGH) for at least 3 months (or 6 months for thyroid replacement therapy) prior to screening.
10. Parent or legal guardian of the child must be willing and able to provide written informed consent and oral assent from child aged between 7 to11 (both inclusive).
ExclusionCriteria
Details
Children will not be eligible for inclusion in this study if any of the following criteria apply:
1. Children born small for gestational age (SGA) (SGA – birth weight and/or birth length less than -2 SDS for gestational age).
2. Malnourished children defined as
BMI less than -2 SDS for age and sex at the time of screening.
Serum albumin and iron below the lower limit of normal (LLN) according to the central laboratory at the time of screening.
3. Presence of anti-hGH antibodies at screening.
4. Children with other cause of short stature such as hypothyroidism or coeliac disease or rickets.
5. Children with more than 1 closed epiphyses at the time of screening.
Note: Evaluation will be performed based on physical examination as per judgment of Investigator and if required additional radiological investigation can be performed.
6. Presence or history of intracranial tumor and intracranial hypertension.
7. Presence or history of any malignant disease.
8. Children with Psychosocial dwarfism.
9. Children with impaired fasting sugar (fasting blood sugar greater than 100 mg/dL or 5.6 mmol/L) at the time of screening.
10. Children with chromosomal abnormalities and medical symptoms including Turner’s syndrome, Noonan syndrome, Prader-Willi syndrome and SHOX mutations/deletions, Laron syndrome, Russell- Silver syndrome and skeletal dysmorphic/dysplasia at the time of screening.
11. Children with known serum positivity for Hepatitis B, C or HIV at the time of screening.
12. History of Tuberculosis.
13. History of drug dependence in the past 1 year prior to screening.
14. Known hypersensitivity to the components of study medication.
15. Participation in any other trial of an investigational agent within 30 days prior to screening.
16. Any clinically significant abnormality apart from growth hormone, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc.
17. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, glucocorticoids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin (DDAVP)).
18. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking chronically a dose greater than 400 μg/day of inhaled budesonide or equivalent as for more than 1 month during the 12 months prior to Visit 1.
19. Presence of contraindications to hGH treatment (Refer prescribing Information of GENOTROPIN7).
20. Females of child-bearing potential
Although children’s who are of child-bearing potential at the time of enrollment will be exclusionary, children who begin menses during the trial may continue.
21. The children and/or the parent/legal guardian are likely to be noncompliant in respect to study conduct.
Method of Generating Random Sequence
Other
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Efficacy Endpoint:
a. Annualized height velocity at Week 29 (absolute and SDS).
29 Weeks
Secondary Outcome
Outcome
TimePoints
1. Safety endpoints:
a. Number of subjects reporting local tolerability events (Patient and Investigator assessment).
b. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
2. Auxology endpoints:
a. Change in height, absolute and SDS from baseline to Week 29.
b. Change of IGF-1 SDS from baseline to Week 29.
3. Immunogenicity endpoint
a. Incidence of Anti-drug antibody (Anti- drug antibody will be further characterized into Binding and Neutralizing antibody).
4. Pharmacokinetic endpoints:
a. For ALT-P1 (Time Frame - From 0 to 168 h)
Cmax of ALT-P1
AUC0-168h of ALT-P1
b. For r-hGH (Time Frame - From 0 to 24h).
Cmax of r-hGH
AUC0-24h of r-hGH
5. Pharmacodynamic endpoints
a. For ALT-P1 (Time Frame - From 0 to 168 h)
Emax of IGF-1, AUC0-168h of IGF-1, Emax of IGFBP-3, AUC0-168h of IGFBP-3
Week 29
Target Sample Size
Total Sample Size="60" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, multicenter,
active-controlled open labelled, multiple-dose, dose finding, and parallel group
trial dosing 60 boys or girls subjects with growth hormone deficiency for 29
weeks. There are 4 arms in the study.
Arm
1: ALT-P1 dose-level 1 (0.4 mg/kg/week)
Arm
2: ALT-P1 dose-level 2 (0.6 mg/kg/week)
Arm
3: ALT-P1 dose-level 3 (0.8 mg/kg/week)
Arm
4: GENOTROPIN® (Somatropin) (0.24 mg/kg/week or 0.034 mg/kg/day) for Injection
Study
Duration: Total study duration for the clinical part will be of around 35 weeks
including 4 weeks of screening period, 28 weeks of treatment period, 1 week of
end of study assessment and 2 weeks of safety follow-up after end of study.
Visit
Schedules:
Screening
visit / Screening Period (Up to 28 days prior to randomization): Visit 1.
Note:
Visit 3 (Week 3/Day 15± 2) will be applicable for Arm 2 and Arm 3 subjects
only. Visit 4 (Week 5/Day 29 ± 2 days) will be applicable for all Arms, however
dose escalation will be applicable for Arm 3 subjects only.
•
End of study#: Visit 10 (Week 29/Day 197+7 days).
•
Safety follow-up: 14 days (±7 days) after end of study visit. Subjects may
visit the study site or it may be performed telephonically.
Dose
and Mode of Administration: Subcutaneous injection.
Test
Product (T):
Arm
1: ALT-P1 dose-level 1 (0.4 mg/kg/week)
Arm
2: ALT-P1 dose-level 2 (0.6 mg/kg/week)
Arm
3: ALT-P1 dose-level 3 (0.8 mg/kg/week)
Reference
Product (R):
Arm
4: GENOTROPIN® (Somatropin) (0.24 mg/kg/week or 0.034 mg/kg/day) for Injection
Study
product will be administered as a s.c. injection once weekly (Week 1/Day
1 to Week 28/Day 190) for Arm 1, 2 and 3 and daily (Day 1 to Day 196)
for Arm 4 as per randomization, using the PEN or vial into the upper arm (ALT-P1 only), thigh,
buttocks, and abdomen as per randomization schedule.
Dosing
will be done at site at Visit 2/ Week 1 (Day 1), Visit 4 (Week 5/Day 29 ±
2 days), Visit 5 (Week 9/Day 57± 2 days), Visit 6 (Week 13/Day 85± 2
days), Visit 7 (Week 17/Day 113± 2 days), Visit 8 (Week 21/Day 141± 2
days) and Visit 9 (Week 25/Day 169 ± 2 days). Rest of the other dosing will be done
at subject’s home by parents/legal guardians.
Dosing
will be done at site at Visit 3 (Week 3/Day 15± 2 days) for Arm 2 and Arm 3
subjects only.
The
dose administration via PEN or vial will be done by investigator or trained
study personnel at site and by parents/legal guardians at home.
PK
and PD (IGF-1 and IGFBP-3) Samples collection: During the study, a total of 17
blood samples (7 ml each) will be collected in each Arm 1, 2 and 3 and 11 blood
samples (7 ml each) will be collected for Arm 4 for pharmacokinetic and
pharmacodynamic analysis.
For
Arm 1, 2 and 3: At
Week 13/ Day 85: 0, 6, 12, 24, 48, 72, 96, 120, 144 and 168 hours. Post
dose blood sample of 48, 72, 96, 120, 144 and 168 hours will be collected as an
ambulatory sample.
Note:
All pre dose sample will be collected within 01 hour prior to dosing. All post
dose samples up to 12 hours will be collected within ± 10 minutes of the
scheduled time and from 24 hours, sample will be collected ± 3 hours of the
scheduled time. All ambulatory sample will be collected within ± 3 hours of the
scheduled time.
For
Arm 4:
Week
13/Day 85: 0, 6, 12, 24 hours.
Pre
dose sample will be collected within 01 hour prior to dosing.
PK/PD
sample at Visit 10 (Week 29/Day 197+7 days) will be collected during end of
study assessment.
Housing
Details: Housing from at least 2 hours before dosing to at least 24 hours post
dose of Week 13/Day 85. Subject will be instructed to visit the clinical site
for 48, 72, 96, 120, 144 and 168 hours post dose of Week 13 blood sample on the
ambulatory basis except Arm 4 subjects.
Food and Fluid Restrictions: Food
and fluid instruction needs to be followed as per protocol.